NM_052839.4:c.870C>G

Variant names:

• chr22-50177582-C-G
• NM_052839.4:c.870C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052839.4(PANX2):​c.870C>G​(p.Ile290Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

Genes affected

PANX2 (HGNC:8600): (pannexin 2) The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 1 are abundantly expressed in central nervous system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 1 may form cell type-specific gap junctions with distinct properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07333371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX2	NM_052839.4	c.870C>G	p.Ile290Met	missense_variant	Exon 2 of 3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.870C>G	p.Ile290Met	missense_variant	Exon 2 of 3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.870C>G	p.Ile290Met	missense_variant	Exon 2 of 4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.*657C>G		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000384148.2
PANX2	ENST00000402472.2	n.*657C>G		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.870C>G (p.I290M) alteration is located in exon 2 (coding exon 2) of the PANX2 gene. This alteration results from a C to G substitution at nucleotide position 870, causing the isoleucine (I) at amino acid position 290 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.026
Sift	Benign	0.19	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.081	B;B
Vest4		0.20
MutPred		0.20		Loss of catalytic residue at I290 (P = 0.0858);Loss of catalytic residue at I290 (P = 0.0858);
MVP		0.21
MPC		1.5
ClinPred		0.13	T
GERP RS		2.3
Varity_R		0.057
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50616011;